Conventional Liver Research Articles

Regulatory T cell therapy: An option to induce operational tolerance in liver transplantation

Regulatory T cells (Treg) may play an important role in operational (clinical) tolerance (OT), a stable graft function without immunosuppression in an otherwise immunocompetent host, that is spontaneously observed in some patients many years after transplantation. Several ongoing clinical trials are currently testing the effects of donor-specific or non-specific Treg infusion with the goal to induce this state of OT a few months after liver transplantation (LT). The preliminary results of two of these trials have been recently published, and raise a number of comments and issues: (1) These two papers demonstrate that a 100 to 1000-fold ex-vivo expansion of Treg is possible in humans after 2 weeks of culture. The optimal human Treg dose is however not clearly established, and might be higher than the dose that would be expected from translating murine data. (2) A lot of concerns are remaining regarding the Treg purity before expansion, the Treg stability during in vitro culture and the in vivo fate of infused cells. A strict monitoring of Treg should thus be done at each step. (3) Since Treg may play a detrimental role in some conditions, such as viral diseases and cancer, potential LT recipients with such diseases should probably be excluded from the initial trials of Treg infusion. (4) The follow-up of tolerant liver recipients should include repeated liver biopsies and detection of autoantibodies and humoral response, in addition to conventional liver graft assessment, in order to prevent the development of immune complications related to immunosuppression withdrawal. (5) The final issue raised by Treg therapy in LT is the choice of the immunosuppressive regimen used before tapering or withdrawal, appropriate to preserve OT establishment.

Pathogenesis of Zika Virus-Associated Embryopathy.

A strong causal association has become evident between Zika virus (ZIKV) infection during pregnancy and the occurrence of fetal growth restriction, microcephaly and eye defects. Circumstantial evidence is presented in this paper in support of the hypothesis that these effects, as well as the Guillain-Barré syndrome, are due to an endogenous form of hypervitaminosis A resulting from ZIKV infection-induced damage to the liver and the spillage of stored vitamin A compounds (“retinoids”) into the maternal and fetal circulation in toxic concentrations. Retinoids are mainly stored in the liver (about 80%) and are essential for numerous biological functions. In higher concentration, retinoids are potentially cytotoxic, pro-oxidant, mutagenic and teratogenic, especially if sudden shifts occur in their bodily distribution. Although liver involvement has not been mentioned specifically in recent reports, conventional liver enzyme tests underestimate the true extent of liver dysfunction. The proposed model could be tested by comparing retinoid concentration and expression profiles in microcephalic newborns of ZIKV-infected mothers and nonmicrocephalic newborn controls, and by correlating these profiles with measures of clinical severity.

The laparoscopic glissonian approach is safe and efficient when compared to conventional laparoscopic liver resection. Results of an observational study over 7 years

The laparoscopic glissonian approach is safe and efficient when compared to conventional laparoscopic liver resection. Results of an observational study over 7 years

Metabolomic Characterizations of Liver Injury Caused by Acute Arsenic Toxicity in Zebrafish.

Arsenic is one of the most common metalloid contaminants in groundwater and it has both acute and chronic toxicity affecting multiple organs. Details of the mechanism of arsenic toxicity are still lacking and profile studies at metabolic level are very limited. Using gas chromatography coupled with mass spectroscopy (GC/MS), we first generated metabolomic profiles from the livers of arsenic-treated zebrafish and identified 34 significantly altered metabolite peaks as potential markers, including four prominent ones: cholic acid, glycylglycine, glycine and hypotaurine. Combined results from GC/MS, histological examination and pathway analyses suggested a series of alterations, including apoptosis, glycogenolysis, changes in amino acid metabolism and fatty acid composition, accumulation of bile acids and fats, and disturbance in glycolysis related energy metabolism. The alterations in glycolysis partially resemble Warburg effect commonly observed in many cancer cells. However, cellular damages were not reflected in two conventional liver function tests performed, Bilirubin assay and alanine aminotransferase (ALT) assay, probably because the short arsenate exposure was insufficient to induce detectable damage. This study demonstrated that metabolic changes could reflect mild liver impairments induced by arsenic exposure, which underscored their potential in reporting early liver injury.

Liver transplantation in acute liver failure: A challenging scenario

Acute liver failure is a critical medical condition defined as rapid development of hepatic dysfunction associated with encephalopathy. The prognosis in these patients is highly variable and depends on the etiology, interval between jaundice and encephalopathy, age, and the degree of coagulopathy. Determining the prognosis for this population is vital. Unfortunately, prognostic models with both high sensitivity and specificity for prediction of death have not been developed. Liver transplantation has dramatically improved survival in patients with acute liver failure. Still, 25% to 45% of patients will survive with medical treatment. The identification of patients who will eventually require liver transplantation should be carefully addressed through the combination of current prognostic models and continuous medical assessment. The concerns of inaccurate selection for transplantation are significant, exposing the recipient to a complex surgery and lifelong immunosuppression. In this challenging scenario, where organ shortage remains one of the main problems, alternatives to conventional orthotopic liver transplantation, such as living-donor liver transplantation, auxiliary liver transplant, and ABO-incompatible grafts, should be explored. Although overall outcomes after liver transplantation for acute liver failure are improving, they are not yet comparable to elective transplantation.

Possible carcinogenic potential of dimethyl dimethoxy biphenyl dicarboxylate in experimental animals.

Dimethyl dimethoxy biphenyl dicarboxylate (DDB) has been extensively used in the treatment of liver diseases accounting for 1–6% of the global disease burden. Cell replication, DNA synthesis, and proliferation, providing significant information about behavior of cells were examined in mice exposed to subchronic administration with DDB. Conventional liver functions specifically gamma-glutamyltransferase (γ-GT), a marker expressing liver canceration was also investigated. Normal mice were allocated into two groups each of 10 mice. The 1st and 2nd groups were treated with DDB in a dose of 50 mg/kg/day, 5 days/week for 1 month and 3 months, respectively. Comparable groups of normal mice were left without treatment as controls. Compared to normal control group, animals receiving DDB for 3 months showed marked elevations of both alanine aminotransferase and γ-GT, significant inhibition in cytochrome P450, a significant increase in the mean ploidy and 4C with moderate to marked increase in S-phase populations and the number of proliferating cell nuclear antigen-positive cells. In conclusion, this is the first report on the potential relationship between the subchronic administration of DDB and the increase in the hepatocyte proliferation, cell replication and DNA synthesis that may raise an alarm regarding possible DDB insult on the biological behavior of cells.

Monitoring Hepatocyte Dysfunction and Biliary Complication After Liver Transplantation Using Quantitative Hepatobiliary Scintigraphy.

The significance of hepatobiliary scintigraphy (HBS) for hepatic graft function assessment was established mostly on retrospective studies and was not widely recognized due to the lack of quantitative data and variation in accuracy. This prospective study was performed to investigate the effectiveness of quantitative HBS for assessing hepatocyte dysfunction and biliary complication in liver transplant recipients.In 57 recipients who had undergone orthotopic liver transplantation, a total of 67 dynamic 99mTc-EHIDA scans were performed and quantitative parameters including the hepatocyte extraction fraction (HEF), time to maximum hepatic radioactivity (Tmax), and time for peak activity to decrease by 50% (T1/2) were calculated. The scintigraphic results based on the 3 parameters were compared against the final diagnosis. A ROC curve analysis was carried out to identify the cutoff value of Tmax for diagnosis of biliary stricture. Correlation between the parameters of postoperative HBS and conventional biochemical liver function indices were also analyzed.Quantitative 99mTc-EHIDA HBS had an overall sensitivity of 94.12% (16/17), specificity of 93.33% (42/45), and diagnostic accuracy of 93.55% (58/62) for detecting hepatocyte dysfunction and biliary complication in liver transplant recipients. The recommended cutoff value of Tmax for diagnosis of post-transplant biliary stricture was set at 15.75 min with a sensitivity of 100.0% and a specificity of 94.0%. The scintigraphic parameters (HEF, Tmax) were statistically significantly associated with the conventional liver function parameters.Quantitative 99mTc-EHIDA HBS offers a noninvasive imaging modality with high sensitivity and specificity to diagnose hepatocyte dysfunction as well as distinguish between patients with or without biliary stricture following liver transplantation. Furthermore, HEF and Tmax values obtained from dynamic HBS show good correlation with conventional liver function parameters.

Video-assisted hepatic abscess debridement

BackgroundPyogenic liver abscesses are currently treated by either percutaneous computer tomography (CT)-guided drainage or by laparoscopic and a conventional liver resection when conservative treatment fails but may be associated with substantial morbidity and mortality. MethodsA minimally invasive technique involving debridement of right liver abscesses was employed using a minimally invasive video-assisted hepatic abscess debridement (VAHD) after unsuccessful percutaneous CT-guided drainage. Clinical data, complication rates and outcomes of patients were recorded retrospectively. ResultsBetween 2011 and 2014, VAHD was performed on 10 patients at two centres with no observed recurrence of a liver abscess. The median age of the patients was 57 years (range 42–78) with a median pre-operative size of a liver abscess of 78 mm (range 40–115). The median operation time was 47 min (range 23–75), and the median postoperative hospital stay was 9 days (range 7–69). One patient developed a subcutaneous abscess that required further surgery. No patient died, and there were no major complications related to the VAHD. ConclusionsVideo-assisted hepatic abscess debridement is a feasible technique that shows promising results for the treatment of a recurrent right liver abscess.

PTU-121 Monitoring changes in hepatic architecture and haemodynamics with quantitative magnetic resonance imaging (MRI) following directly-acting antiviral therapy in hepatitis C patients with decompensated cirrhosis

Introduction Directly-acting antiviral (DAA) therapy achieves sustained virological response (SVR) in over 90% of those with chronic hepatitis C (CHC), but even in those with SVR, the risk for liver related morbidity and mortality persists albeit at a lower level. It is hypothesised that the residual risk of liver related outcome in those with SVR is related to the progression or non-regression of structural and haemodynamic changes of advanced liver disease at the time of HCV therapy. Here, we investigate the effect of DAAs on the hepatic architecture and splanchnic haemodynamics in patients with decompensated cirrhosis, using quantitative MRI techniques. Method We prospectively recruited patients receiving DAAs for CHC related decompensated cirrhosis from the East Midlands hub of the Early Access Programme commissioned by NHS England. MRI was performed before and at the end of a 12-week treatment with Daclatasvir, Sofosbuvir and Ribavarin. A respiratory-triggered inversion recovery scheme was used to measure the longitudinal (T1) relaxation time of the liver employing a fat suppressed Echo Planar Imaging-acquisition. Phase-contrast (PC)-MRI was used to assess the velocity, area and bulk flow in the splanchnic circulation without any intravenous contrast agents. Results 9 patients have undergone baseline and post-treatment MR scans and end-of-treatment response (EOTR) was achieved in all 9 patients, but one patient has had virologic relapse. There was a significant reduction in the T1 relaxation time in patients with SVR (baseline T1: 765 ± 112 ms; post-treatment 737 ± 118 ms; p = 0.043) (Figure 1). There were no significant changes in the hepatic artery, portal vein, superior mesenteric artery and splenic artery flow. The changes in the Model for End-Stage Liver Disease (MELD) and United Kingdom Model for End-Stage Liver Disease (UKELD) score are shown in Table 1. Conclusion Treatment of decompensated CHC related cirrhosis with DAA is associated with early improvement in the MR markers of liver architecture. These early changes are likely to reflect the reduction in the inflammation associated with EOTR and is evident before any improvement in conventional liver function tests. This novel quantitative MR methodology will allow us to non-invasively monitor HCV related liver disease. Disclosure of interest None Declared.

Liver enzyme abnormalities in taking traditional herbal medicine in Korea: A retrospective large sample cohort study of musculoskeletal disorder patients

Ethnopharmacological relevanceThe objective of this study is to report the incidence of liver injury from herbal medicine in musculoskeletal disease patients as large-scale studies are scarce. Considering that herbal medicine is frequently used in patients irrespective of liver function in Korea, we investigated the prevalence of liver injury by liver function test results in musculoskeletal disease patients. Materials and methodsOf 32675 inpatients taking herbal medicine at 7 locations of a Korean medicine hospital between 2005 and 2013, we screened for liver injury in 6894 patients with liver function tests (LFTs) at admission and discharge. LFTs included t-bilirubin, AST, ALT, and ALP. Liver injury at discharge was assessed by LFT result classifications at admission (liver injury, liver function abnormality, and normal liver function). In analyses for risk factors of liver injury at discharge, we adjusted for age, sex, length of stay, conventional medicine intake, HBs antigen/antibody, and liver function at admission. ResultsA total 354 patients (prevalence 5.1%) had liver injury at admission, and 217 (3.1%) at discharge. Of the 354 patients with liver injury at admission, only 9 showed a clinically significant increase after herbal medicine intake, and 225 returned to within normal range or showed significant liver function recovery. Out of 4769 patients with normal liver function at admission, 27 (0.6%) had liver injury at discharge. In multivariate analyses for risk factors, younger age, liver function abnormality at admission, and HBs antigen positive were associated with injury at discharge. ConclusionsThe prevalence of liver injury in patients with normal liver function taking herbal medicine for musculoskeletal disease was low, and herbal medicine did not exacerbate liver injury in most patients with injury prior to intake.

Use of liver breath tests to assess severity of nonalcoholic fatty liver disease.

As the prevalence of obesity and insulin-resistance continues to increase in the general population, nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions, thus becoming one of the leading causes of chronic liver disease worldwide. It may present as simple steatosis (NAFL) or steatohepatitis (NASH), which in turn may develop fibrosis and ultimately cirrhosis. Conventional biochemical liver test and radiological investigations are not able to provide reliable information on liver functional reserve, and liver biopsy remains the gold standard to stage NAFLD, differentiate simple steatosis from NASH, and grade fibrosis. However, liver biopsy has some limitations, and is not preferred by patients due to its invasiveness. Thus, non-invasive assessment of disease stage by using liver breath tests - which are based on hepatic clearance of non-radioactive stable (13)C-labelled drugs - may be of interest to stage disease and assess patients prognosis due to good accuracy and repeatability. These substrates are orally administered and are cleaved by enzymes specifically located in the liver thus reflecting either the microsomal, cytosolic, or mitochondrial functions. (13)C-Breath Tests have been initially oriented to differentiate broad categories of patients and more recently to refine stage differentiation in patients with early stages of liver disease. In NAFLD patients, (13)C-BTs were able to distinguish simple steatosis from NASH and had good correlation with both histological fibrosis stage and biochemical markers of fibrogenesis. Although promising results have been achieved in this field, their use in clinical practice is still restricted to a specialized niche. However, concordant data from literature conferred to (13)C-Breath Tests a potential role in providing punctual and longitudinal evaluation of patients, identifying those patients where liver biopsy may selectively be performed to stage disease, monitoring and predicting therapeutic response.

The safety and efficacy of approaches to liver resection: a meta-analysis.

Background:The aim of this study is to compare the safety and efficacy of conventional laparotomy with those of robotic and laparoscopic approaches to hepatectomy.Database:Independent reviewers conducted a systematic review of publications in PubMed and Embase, with searches limited to comparative articles of laparoscopic hepatectomy with either conventional or robotic liver approaches. Outcomes included total operative time, estimated blood loss, length of hospitalization, resection margins, postoperative complications, perioperative mortality rates, and cost measures. Outcome comparisons were calculated using random-effects models to pool estimates of mean net differences or of the relative risk between group outcomes. Forty-nine articles, representing 3702 patients, comprise this analysis: 1901 (51.35%) underwent a laparoscopic approach, 1741 (47.03%) underwent an open approach, and 60 (1.62%) underwent a robotic approach. There was no difference in total operative times, surgical margins, or perioperative mortality rates among groups. Across all outcome measures, laparoscopic and robotic approaches showed no difference. As compared with the minimally invasive groups, patients undergoing laparotomy had a greater estimated blood loss (pooled mean net change, 152.0 mL; 95% confidence interval, 103.3–200.8 mL), a longer length of hospital stay (pooled mean difference, 2.22 days; 95% confidence interval, 1.78–2.66 days), and a higher total complication rate (odds ratio, 0.5; 95% confidence interval, 0.42–0.57).Conclusion:Minimally invasive approaches to liver resection are as safe as conventional laparotomy, affording less estimated blood loss, shorter lengths of hospitalization, lower perioperative complication rates, and equitable oncologic integrity and postoperative mortality rates. There was no proven advantage of robotic approaches compared with laparoscopic approaches.

Advances in reduced port laparoscopic liver resection.

Reduced port surgery has been attracting attention in the field of minimally invasive surgery. Although the use of SILS is becoming widespread, technical difficulty has delayed its adoption for laparoscopic liver resection. Recently, advances in laparoscopic liver resection have been made in tandem with advances in surgical skill and devices. The main driver in conventional laparoscopic liver resection's evolution to become less surgically invasive seems to be single-incision laparoscopic liver resection (SILLR). To date, most reports on SILLR have been single case reports or case series. Only a few cohort studies on conventional laparoscopic surgery and SILLR have been conducted. Recent reports have described the use of SILLR for well-localized lesions and solitary tumors located in the anterolateral segments of the liver or left liver lobe, but its application remains limited to partial resection and left lateral sectionectomy. The feasibility and safety of SILLR have been demonstrated, but additional work is needed for standardization of the procedure.

Functional assessment versus conventional volumetric assessment in the prediction of operative outcomes after major hepatectomy

In this study we examined whether conventional future remnant liver volume (FR volume) or function (FR function) better predicted the operative outcome after major hepatectomy. Of 510 patients who underwent hepatectomy for various indications, 133 patients with major hepatectomy were enrolled in this study. FR volume and the corresponding FR function routinely were measured with a 99mTc-GSA scintigraphy single-proton emission computed tomography fusion system. FR function was defined as the future remnant liver uptake ratio of 99mTc-GSA per whole liver by single-proton emission computed tomography. FR volume or function in cases with insufficient FR volume or function required for major hepatectomy were defined as marginal. Morbidity, liver dysfunction-related morbidity, and mortality after major hepatectomy occurred in 40 (30%), 10 (7.5%), and 8 (5.7%) patients, respectively. Thirty-two of the 133 patients were diagnosed as marginal using FR volume, but only 11 patients were diagnosed as marginal using FR function. These results indicated that 21 patients (16%) were switched to the safe group using functional assessment. Operative outcomes in patients with safe FR function (n = 122) were equivalent to those of patients with safe FR volume (n = 101), but patients with marginal FR function (n = 11) had substantially worse outcomes than patients with marginal FR volumes (n = 32). Logistic regression analysis identified marginal FR function, but not volume, as a risk factor for worse operative outcome after major hepatectomy. Portal vein embolization induced the substantially greater FR function compared with FR volume. Although liver volume equally corresponds to liver function under normal conditions, liver cirrhosis was greatly associated with the major discrepancy (more than 10%) in patients without portal vein embolization. Functional assessment for future remnant liver identified patients who were eligible for curative hepatectomy despite a marginal status based on conventional volumetric assessment. Thus, marginal FR function is a better predictor of operative outcome after major hepatectomy than FR volume, especially in patients with nonhealthy liver.

Serum 25-hydroxyvitamin D levels are associated with carotid atherosclerosis in normotensive and euglycemic Chinese postmenopausal women: the Shanghai Changfeng study.

BackgroundThe role of serum 25-hydroxyvitamin D (25 (OH) D) in atherogenesis is unclear. We investigated whether the 25 (OH) D is independently associated with the carotid intima–media thickness (CIMT) and carotid plaques in normotensive and euglycemic postmenopausal women.MethodsA total of 671 normotensive and euglycemic postmenopausal women (mean age, 58.8 years) were enrolled from the Changfeng Study. A standard interview, anthropometrics measurements and laboratory analyses were performed for each participant. Bilateral CIMTs were measured using ultrasonography, and the presence of carotid plaques was assessed. The serum 25 (OH) D was measured using electrochemiluminescence immunoassay.ResultsSerum 25 (OH) D was 43.6 ± 18.2 nmol/L in the postmenopausal women. Compared with subjects with 25 (OH) D in the first, second and third quartiles, subjects with 25 (OH) D in the fourth quartile had decreased CIMT and prevalence of carotid plaque (0.684 ± 0.009 mm vs 0.719 ± 0.009 mm, 0.708 ± 0.009 mm and 0.709 ± 0.009 mm; 10.8% vs 19.0%, 14.8% and 16.8%, respectively). After adjusting for conventional CVD risk factors, PTH, liver and renal function, postmenopausal women with 25 (OH) D in the fourth quartile still had lower CIMT than those in the first, second and third quartiles (p = 0.039) and the subjects in the fourth quartile had a 0.421-fold decreased risk of carotid plaques relative to those in the lowest quartile (95% confidence interval 0.209 to 0.848).ConclusionsThese results suggest serum 25 (OH) D is independently and inversely associated with carotid atherosclerosis in postmenopausal women with normal blood pressure and normal glucose tolerance.

Clinical research on microecologic treatment combined enteral nutrition for hepatic encephalopathy

To evaluate the effect of microecologic treatment combined enteral nutrition on serum endotoxin, tumor necrosis factor-α (TNF-α), interleukin-18 (IL-18), blood ammonia levels and nutritional status in patients with hepatic encephalopathy. 60 patients with hepatic encephalopathy were allocted randomly into 3 groups, on the basis of conventional liver protective therapy and uragogue with one group given probiotics plus enteral nutrition, one given probiotics only, and the 3rd group given intravenous nutrition. The whole course of treatment was four weeks. Serum levels of endotoxin, TNF-α, IL-18, ammonia and albumin were determined before and on the 7th and 14th day after treatment. The levels of serum endotoxin, TNF-α, IL-18 and blood ammonia in the combined treatment group decreased remarkably after treatment, while the level of serum albumin elevated markedly. The difference was significant at statistics as compared with the only probiotics group and intravenous nutrition group (P < 0.05). Microecologic treatment combined enteral nutrition could effectively reduce blood ammonia and serum endotoxin levels, protect intestinal mucosal barrier, as well as improve nutritional status of patients with hepatic encephalopathy, which was considered as a safe and efficient therapy.

Complete protocol for slow-spinning high-resolution magic-angle spinning NMR analysis of fragile tissues.

High-resolution magic-angle spinning (HR-MAS) nuclear magnetic resonance (NMR) is an essential tool to characterize a variety of semisolid systems, including biological tissues, with virtually no sample preparation. The "non-destructive" nature of NMR is typically compromised, however, by the extreme centrifugal forces experienced under conventional HR-MAS frequencies of several kilohertz. These features limit the usefulness of current HR-MAS approaches for fragile samples. Here, we introduce a full protocol for acquiring high-quality HR-MAS NMR spectra of biological tissues at low spinning rates (down to a few hundred hertz). The protocol first consists of a carefully designed sample preparation, which yields spectra without significant spinning sidebands at low spinning frequency for several types of sample holders, including the standard disposable inserts classically used in HR-MAS NMR-based metabolomics. Suppression of broad spectral features is then achieved using a modified version of the recently introduced PROJECT experiment with added water suppression and rotor synchronization, which deposits limited power in the sample and which can be suitably rotor-synchronized at low spinning rates. The performance of the slow HR-MAS NMR procedure is demonstrated on conventional (liver tissue) and very delicate (fish eggs) samples, for which the slow-spinning conditions are shown to preserve the structural integrity and to minimize intercompartmental leaks of metabolites. Taken together, these results expand the applicability and reliability of HR-MAS NMR spectroscopy. These results have been obtained at 400 and 600 MHz and suggest that high-quality slow HR-MAS spectra can be expected at higher magnetic fields using the described protocol.

UltraFast Doppler ultrasonography for hepatic vessels of liver recipients: preliminary experiences.

Purpose:The purpose of this study was to investigate the value of UltraFast Doppler ultrasonography (US) for evaluating hepatic vessels in liver recipients.Methods:Thirty-nine liver Doppler US sessions were conducted in 20 liver recipients. Each session consisted of UltraFast and conventional liver Doppler US in a random order. We compared the velocities and phasicities of the hepatic vessels, duration of each Doppler study, occurrence of technical failures, and differences in clinical decisions.Results:The velocities and resistive index values of hepatic vessels showed a strong positive correlation between the two Doppler studies (mean R=0.806; range, 0.710 to 0.924). The phasicities of the hepatic vessels were the same in both Doppler US exams. With respect to the duration of the Doppler US exam, there was no significant difference between the UltraFast (251±99 seconds) and conventional (231±117 seconds) Doppler studies (P=0.306). In five poor breath-holders, in whom the duration of conventional Doppler US was longer, UltraFast Doppler US (272±157 seconds) required a shorter time than conventional Doppler US (381±133 seconds; P=0.005). There was no difference between the two techniques with respect to technical failures and clinical decisions.Conclusion:UltraFast Doppler US is clinically equivalent to conventional Doppler US with advantages for poor breath-holders during the post-liver transplantation work-up.

A New Method for Measuring the Speed of Sound in Rat Liver ex Vivo Using an Ultrasound System: Correlation of Sound Speed with Fat Deposition

The speed of sound correlates well with the fat content of the liver. Therefore, non-invasive quantification of sound speed in the liver might be of diagnostic value. Here we describe a new non-invasive method that would be clinically applicable for measurement of sound speed in the liver. Sprague–Dawley rats were divided into two groups: a control group and a fatty liver group prepared by keeping the rats on a choline-deficient diet for 6 wk. The livers were subjected to pathologic and biochemical analysis; the speed of sound through the liver tissue was measured using our proposed method and a pulser–receiver as standard. Our results indicated that use of the proposed method makes it feasible to diagnose fatty liver with good accuracy on the basis of sound speed. This approach would have considerable potential for non-invasive diagnosis of fatty liver and would be a valuable adjunct to conventional liver diagnostic procedures.

Quantifying Rigid and Nonrigid Motion of Liver Tumors During Stereotactic Body Radiation Therapy

To quantify rigid and nonrigid motion of liver tumors using reconstructed 3-dimensional (3D) fiducials from stereo imaging during CyberKnife-based stereotactic body radiation therapy (SBRT). Twenty-three liver patients treated with 3 fractions of SBRT were used in this study. After 2 orthogonal kilovoltage images were taken during treatment, the 3D locations of the fiducials were generated by the CyberKnife system and validated using geometric derivations. A total of 4824 pairs of kilovoltage images from start to end of treatment were analyzed. For rigid motion, the rotational angles and translational shifts were reported by aligning 3D fiducial groups from different image pairs, using least-squares fitting. For nonrigid motion, we quantified interfractional tumor volume variations by using the proportional volume derived from the fiducials, which correlates to the sum of interfiducial distances. The individual fiducial displacements were also reported (1) after rigid corrections and (2) without angle corrections. The proportional volume derived by the fiducials demonstrated a volume-increasing trend in the second (101.9% ± 3.6%) and third (101.0 ± 5.9%) fractions among most patients, possibly due to radiation-induced edema. For all patients, the translational shifts in left-right, anteroposterior, and superoinferior directions were 2.1 ± 2.3 mm, 2.9 ± 2.8 mm, and 6.4 ± 5.5 mm, respectively. The greatest translational shifts occurred in the superoinferior direction, likely due to respiratory motion from the diaphragm. The rotational angles in roll, pitch, and yaw were 1.2° ± 1.8°, 1.8° ± 2.4°, and 1.7° ± 2.1°, respectively. The 3D individual fiducial displacements with rigid corrections were 0.2 ± 0.2 mm and increased to 0.5 ± 0.4 mm without rotational corrections. Accurate 3D locations of internal fiducials can be reconstructed from stereo imaging during treatment. As an effective surrogate to tumor motion, fiducials provide a close estimation of both rigid and nonrigid motion of liver tumors. The reported displacements could be further utilized for tumor margin definition and motion management in conventional linear accelerator-based liver SBRT.